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      Application of Metabolomics in Alzheimer’s Disease

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          Abstract

          Progress toward the development of efficacious therapies for Alzheimer’s disease (AD) is halted by a lack of understanding early underlying pathological mechanisms. Systems biology encompasses several techniques including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Metabolomics is the newest omics platform that offers great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual’s metabolome reflects alterations in genetic, transcript, and protein profiles and influences from the environment. Advancements in the field of metabolomics have demonstrated the complexity of dynamic changes associated with AD progression underscoring challenges with the development of efficacious therapeutic interventions. Defining systems-level alterations in AD could provide insights into disease mechanisms, reveal sex-specific changes, advance the development of biomarker panels, and aid in monitoring therapeutic efficacy, which should advance individualized medicine. Since metabolic pathways are largely conserved between species, metabolomics could improve the translation of preclinical research conducted in animal models of AD into humans. A summary of recent developments in the application of metabolomics to advance the AD field is provided below.

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          Most cited references132

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          Innovation: Metabolomics: the apogee of the omics trilogy.

          Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.
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            Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.

            Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer beta-amyloid (Abeta) precursor protein containing a Lys670 --> Asn, Met671 --> Leu mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age but showed impairment by 9 to 10 months of age. A fivefold increase in Abeta(1-40) and a 14-fold increase in Abeta(1-42/43) accompanied the appearance of these behavioral deficits. Numerous Abeta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of Abeta. The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.
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              Sugar for the brain: the role of glucose in physiological and pathological brain function.

              The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/489267
                URI : http://frontiersin.org/people/u/72222
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                12 January 2018
                2017
                : 8
                : 719
                Affiliations
                [1] 1Mitochondrial Neurobiology and Therapeutics Laboratory, Department of Neurology, Mayo Clinic , Rochester, MN, United States
                [2] 2Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic , Rochester, MN, United States
                Author notes

                Edited by: Mark Mapstone, University of California, Irvine, United States

                Reviewed by: Robert Friedland, University of Louisville, United States; Elena Marcello, Università degli Studi di Milano, Italy

                *Correspondence: Eugenia Trushina, trushina.eugenia@ 123456mayo.edu

                Specialty section: This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2017.00719
                5770363
                29375465
                26d7720e-ab48-4827-b7f6-9937c762f9a0
                Copyright © 2018 Wilkins and Trushina.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 October 2017
                : 13 December 2017
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 200, Pages: 20, Words: 17349
                Funding
                Funded by: National Institute on Aging 10.13039/100000049
                Award ID: AG55549
                Categories
                Neuroscience
                Review

                Neurology
                alzheimer’s disease,metabolomics,lipidomics,biomarkers,animal models of alzheimer’s disease

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